Medical contact shock freezer

ABSTRACT

A medical contact shock freezer adapted for fast freezing a plurality of individual bags containing a medical liquid has the contact surface of its upper freezing plate arranged at an angle of at least 2° to the horizontal.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of pending U.S. application Ser. No.16/616,189 filed on Nov. 29, 2019, as the U.S. National Stage Entry ofPCT Application No. PCT/EP2018/063409 filed May 22, 2018, claimingpriority to United Kingdom Application No. 170881504 filed on Jun. 2,2017, the entireties of each of which is hereby incorporated byreference.

BACKGROUND OF THE INVENTION

This invention relates to a medical contact shock freezer adapted forfast freezing a plurality of individual bags containing a medicalliquid, for example blood plasma, a biological preparation or apharmaceutical preparation, and to a method of freezing medical liquids.

A known medical contact shock freezer is described in EP1596899, thecontents of which are hereby incorporated by reference. Appropriatefeatures described in EP1596899 may be used in relation to the presentinvention.

Blood plasma bags are commonly used to store, transport and dispenseblood plasma and comprise flexible plastics walls which may be made ofpolyethylene, polypropylene or plasticized PVC. In order to ensureplasma quality, once the plasma has been obtained, for example byplasmapheresis, it is desirable for the plasma contained within afilled, sealed plasma bag to be completely frozen to a temperature of−30° C. or less within a short time period. The step of rapidly freezingthe plasma, for example from its collection temperature or from roomtemperature to −30° C., is facilitated by use of a contact shock freezerin which a plurality of plasma bags are pressed between cooling plateswhich are chilled by a circulating coolant. Once frozen, the plasma bagsare transferred to a medical storage freezer which may be maintained ata temperature of −30° C., −50° C. or below.

SUMMARY OF THE INVENTION

In accordance with one of its aspects, the present invention provides amedical contact shock freezer in accordance with claim 1. Other aspectsare defined in independent claims. The dependent claims define preferredor alternative features.

It has surprising been found that the reliability of and/or timerequired for freezing a plurality of individual bags in a medical shockfreezer can be improved by arranging the contact surface of the upperfreezing plate at an angle to the horizontal and/or angling the bagscontaining the medical liquid. Whilst not wishing to be bound by theory,it is believed that although bags containing blood plasma are intendedto be sealed without the presence of any air in the bag, even whenfollowing good practice, it is possible for at least some plasma bagswithin a plurality of bags being prepared together to contain some air.When the plasma bags are loaded into a shock freezer having horizontalcooling plates such that the plasma bags are horizontal, any plasma bagcontaining air will have an air pocket formed between the plasma and itsupper plastics wall and positioned towards the centre of the upper wallof the bag. Despite the pressure applied to the plasma bags by thecooling plates, it is believed that such an air bubble significantlyreduces the transfer of heat from the plasma to the cooling plates andthus slows down freezing of the plasma in any bag in which such an airbubble is present. It has surprisingly been found that by angling thebags and/or the upper and/or lower freezing plate, any air bubblespresent are displaced away from the centre of the plasma bag and areless disruptive to the desired freezing cycle. The ability toautomatically compensate for even occasional and undesired presence ofan air bubble in one or more bag being frozen is particularlysignificant for medical liquids in respect of which it is important toensure that each bag being frozen is frozen to a desired temperature ina desired time. The invention may thus be used, for example, to improvereliability of the process of freezing a medical liquid and/or reducethe necessity of relying upon, for example, an increase in freezing timeor a reduction in the temperature of the freezing plates to ensureconformity.

Each bag to be frozen may contain a quantity of medical liquid, notablyplasma, which is ≥150 ml, ≥200 ml or ≥250 ml and/or ≤1000 ml, ≤850 ml,≤500 ml or ≤450 ml or ≤350 ml. Each bag may have a nominal volume of 500ml; in this case, each bag may contain about 250 ml of medical liquid,notably plasma, for example from a whole blood donation of 500 ml. Eachbag may have a nominal volume of 1000 ml; in this case, each bag maycontain about 850 ml of medical liquid, notably plasma, for example fromplasmapheresis.

The or each pair of freezing plates may define an operating surface,that is to say a surface at which individual bags can be arranged forfreezing, which has an area ≥0.25 m², ≥0.3 m², ≥0.4 m², ≥0.5 m², ≥0.55m², ≥0.7 m² or ≥0.8 m² and/or ≤1.4 m², ≤1.3 m²≤1.2 m² or ≤1 m². Forexample, the or each pair of freezing plates may define an operatingsurface which has:

-   -   a width that is ≥0.4 m, ≥0.5, ≥0.6 m, ≥0.7 m, ≥0.8 m or ≥0.9 m        and/or ≤1.6 m, ≤1.5 m, ≤1.2 m or less than 1.1 m; and/or    -   a depth that is ≥0.5 m, ≥0.6 m and/or ≤1.1 m, ≤1 m or ≤0.9 m.

Such dimensions facilitate loading of the bags by an operator. The oreach pair of freezing plates may be configured and/or dimensioned tosimultaneously freeze ≥9 bags, ≥12 bags, ≥16 bags, ≥21 bags or ≥30 bagsand/or ≤50, ≤48, ≤40 or ≤32 bags, notably 500 ml nominal volume bags.For example, the or each pair of freezing plates may be configuredand/or dimensioned to simultaneously freeze 3, 4, 5, 6, 7 8 or 9 rows ofbags arranged across its width with 3 or 4 bags in each row arrangedalong its depth, notably bags having a nominal volume of 500 ml.Particularly in the case of bags containing between 150 ml and 355 ml ofmedical liquid to be frozen, individual bags may be stacked one onanother to form i) a first layer of bags, each bag in the first layerhaving a lower side which is in contact with the contact surface of alower freezing plate of a pair of freezing plates and ii) a second layerof bags, each bag in the second layer having a lower side which sits onan upper side of a bag in the first layer of bags and an upper sidewhich, in the freezing position, is in contact with the contact surfaceof an upper freezing plate of the pair of freezing plates. Preferably,each bag has an outlet from which the medical liquid will be extracted,and the outlet is arranged facing the rear of the shock freezer.

Each freezing plate may be configured to operate at a temperature whichis ≤−40° C., ≤−45° C. or ≤−50° C. This provides rapid shock freezing.This operating temperature is preferably reached with 30 minutes, within25 minutes or within 20 minutes of initial operation of the shockfreezer. The freeze time required to attain a core temperature of themedical liquid in the bags of −30° C. is preferably ≤60 minutes, ≤50minutes or more preferably ≤45 minutes, notably when the or each pair offreezing plates are fully loaded with bags to be frozen at an initialtemperature of 20° C., notably bags each containing ≥200 ml or ≤250 mland/or ≤1000 ml or ≤850 ml of blood plasma. Preferably, such a freezingperformance is achieved with an initial temperature which is ≥25° C.,≥30° C. or ≥32° C. and/or ≤35° C.

It has been found that an improvement in the freezing cycle can beobtained with a fairly small angle of the upper and/or lower contactsurfaces of the freezing plate, for example an angle of about 2° to thehorizontal. An angle of between 3° and 10°, notably 5°, to thehorizontal provides an advantageous effect combined with a configurationwhich facilitates loading and unloading of the bags. Nevertheless, theangle may be increased and may be ≥about 2° and/or ≤about 30°, ≤about20° or ≤about 15°. At higher angles it is advantageous to configure thecontact surface of the lower freezing plate to reduce the chance of thebags slipping along the inclined surface. The contact surface(s) of thefreezing plate(s) preferably incline such that it rear portion is higherthat its front portion; this facilitates loading and unloading of theplasma bags. Alternatively, the contact surface(s) of the freezingplate(s) may be inclined such that its rear portion is lower that itsfront portion.

Clamping of the individual bags between the contact surface of the upperand lower freezing plates is preferably affected in such a way that thesurfaces of the bags in contact with the freezing plates are flattened;this increases the contact area and improves heat transfer. Sufficientforce may be applied to clamp the bags between the freezing plates suchthat a pressure which is ≥0.1 bar or ≥0.2 bar and/or ≤0.5 bar isgenerated in the medical liquid within the bag.

The movement of the upper and/or lower freezing plate from the loadingposition to the freezing position is preferably a linear movement,notably a vertical linear movement, without rotation of the plate. Thisfacilitates accurate clamping of the plurality of bags between theplates. Preferably, the contact surfaces of upper and lower freezingplates of a pair of freezing plates are parallel in their freezingposition and remain parallel during movement between the loading and thefreezing position. This further facilitates accurate clamping of theplurality of bags. The use of parallel and preferably planer contactsurfaces of upper and lower freezing plates of a pair of freezing platesis also advantageous when it is desired for the shock freezer to beuseable in a configuration having two layers the bags arranged between apair of freezing plates. Preferably, the angle of each freezing plate tothe horizontal is fixed, that is to say this angle does not change; eachfreezing plate may be fixed in rotation so that it cannot rotate. Atleast one of the upper and lower freezing plates of a pair of freezingplates may be associated with a linear drive to affect its movement fromthe loading to the freezing position, for example one or more pneumaticor hydraulic cylinders, notably a pair of spaced cylinders, for examplearranged at opposite sides of the freezing plate. The movement may beguided by a linear guide arrangement, for example comprising a linearguide arranged at each of the left and right sides of the freezingplate. Each linear guide may comprise a pair of, preferably vertical,tubular guide elements which together guide the movement.

Preferably, one of the upper and lower freezing plates of a pair offreezing plates is fixed and does not move; this provides a mechanicallyadvantageous arrangement. An arrangement in which the shock freezercomprises:

-   a first pair of upper and lower freezing plates and a second pair of    upper and lower freezing plates, the first pair being arranged above    the second pair;-   in which the first pair of upper and lower freezing plates comprises    an immobile lower freezing plate and a moveable upper freezing    plate; and-   in which the second pair of upper and lower freezing plates    comprises an immobile upper freezing plate and a moveable lower    freezing plate;-   and notably in which the lower freezing plate of the first pair of    freezing plates and the upper freezing plate of the second pair of    freezing plates are provided by a single, integrated freezing plate,    provides a compact and convenient arrangement for providing two    pairs of freezing plates to enable simultaneous freezing of a large    number of individual bags whilst minimising the footprint of the    shock freezer and facilitating loading and unloading.

Arranging the contact surfaces of the upper and lower freezing plates asplanar contact surfaces, preferably parallel, planar contact surfaces,facilitates use of the shock freezer with bags of different sizes andallows for use of mechanically simple clamping of the bags.

The shock freezer is provided with suitable cooling apparatus to coolthe freezing plates to their desired temperature, for example a coolingfluid provided in a cooling circuit comprising a compressor, acondenser, and an evaporator. Preferably, the cooling apparatus isarranged within the footprint of the cooling plates. The power rating ofthe shock freezer may be ≥1.5 kW, ≥2 kW, ≥2.5 kW or ≥4 kW and/or ≤0 kWor ≤8 kW.

BRIEF DESCRIPTION OF THE DRAWINGS

An embodiment of the invention will now be described, by way of exampleonly, with reference to the accompanying drawings, of which:

FIG. 1 is schematic front view of a shock freezer with its freezingplates in their loading position;

FIG. 2 is a schematic front view of the shock freezer with its freezingplates in their freezing position; and

FIG. 3 is a schematic side view of the freezing plates in their freezingposition.

DETAILED DESCRIPTION

The illustrated contact shock freezer 10 comprises: a first pair 11 ofupper 21 and lower 22 freezing plates; and a second pair 12 of upper 31and lower 32 freezing plates; the first pair 11 being arranged above thesecond pair 12. The lower freezing plate 22 of the first pair offreezing plates 11 and the upper freezing plate 31 of the second pair offreezing plates 12 are provided by a single, immobile, integratedfreezing plate 13.

In use, with each pair 11, 12 of freezing plates in its loading position(FIG. 1), a first series of plasma bags to be frozen is arranged in rows(the front bag 41, 42, 43 of each row being illustrated in FIG. 1)between the upper 21 and lower 22 freezing plates of the first pair offreezing plates 11 by being placed on an operating surface provided bythe lower freezing plate 22 by an operator standing in front of thefreezer 10. A second series of plasma bags to be frozen is similarlyarranged in rows (the front bag 51, 52, 53 of each row being illustratedin FIG. 1) between the upper 31 and lower 32 freezing plates of thesecond pair of freezing plates 12 by being placed on an operatingsurface provided the lower freezing plate 32 by an operator standing infront of the freezer 10. Each pair 11, 12 of freezing plates is thenmoved from its loading position (FIG. 1) to its freezing position (FIG.2) in the following way: the upper freezing plate 21 of the first pairof freezing plates 11 is moved vertically downwards by a pair ofvertically arranged hydraulic cylinders 61, 62 arranged at the left side61 and right side 62 of the upper freezing plate to clamp the firstseries of plasma bags to be frozen between a contact surface 23 of theupper freezing plate 21 and a contact surface 24 of the lower freezingplate 22; and the lower freezing plate 32 of the second pair 12 offreezing plates is moved vertically upwards by a pair of verticallyarranged hydraulic cylinders 63, 64 arranged at the left side 63 andright side 64 of the lower freezing plate 32 to clamp the second seriesof plasma bags to be frozen between a contact surface 33 of the upperfreezing plate 31 and a contact surface 34 of the lower freezing plate32. In the freezing position (FIG. 2), with the plasma bags 41, 42, 43,51, 52, 53 clamped between their respective freezing plates, the plasmain the bags is frozen from a temperature of about 20° C. to atemperature of −30° C. in a time of about 40 minutes. Once the plasmabags have been frozen, each pair of freezing plates 11, 12 is moved fromits freezing position (FIG. 2) to its loading position (FIG. 1) and theplasma bags are removed by an operator standing at the front of theshock freezer 10 and placed in cold storage.

The illustrated contact shock freezer 10 is shown schematically withnine plasma bags arranged between each pair 11, 12 of freezing plates.The first pair 11 of freezing plates 11 has three lines of plasma bagsarranged across its width (of which the front bag 41, 42, 43 of eachline is illustrated in FIG. 1 and FIG. 2) and three lines of plasma bagsarranged across its depth (of which the left side bag 41, 44, 47 of eachrow is illustrated in FIG. 3). The illustrated arrangement for thesecond pair 12 of freezing plates is similar. Flattening and compressionof the plasma bags in the freezing position is schematically illustratedin FIG. 2.

Contact surfaces 23, 24 of the first pair 11 of freezing plates 21, 22are each planar and parallel to each other and are arranged to slopeupwardly from the front 71 to the rear 72 of the shock freezer 10 at anangle α to the horizontal. Similarly, contact surfaces 33, 34 of thesecond pair 12 of freezing plates 31, 32 are each planar and parallel toeach other and are arranged to slope upwardly from the front 71 to therear 72 of the shock freezer 10 at an angle α to the horizontal. Theangle α is preferably between about 2° and about 10°, for example about5° but has been shown in an exaggerated fashion in FIG. 3 forillustrative purposes.

As shown in FIG. 3, each bag is held in an angled bag configuration atan angle α to the horizontal, that is to say, a plane passing centrallythrough each bag with respect to its upper and lower walls has an angleα to the horizontal.

1-15. (canceled)
 16. A medical contact shock freezer adapted for fastfreezing a plurality of individual bags containing a medical liquid, theindividual bags being arranged side by side, adjacent to each other, inwhich the contact shock freezer comprises a pair of freezing platescomprising an upper freezing plate and a lower freezing plate; in whichone of the upper and lower freezing plates of the pair of freezingplates is a fixed freezing plate which is fixed and does not move; inwhich the other one of the upper and lower freezing plates of the pairis a moveable freezing plate which is moveable to define i) a loadingposition in which sufficient separation is provided between the freezingplates to load or unload the individual bags between the freezing platesand ii) a freezing position in which each individual bag is in contactwith and is clamped between a contact surface of the upper freezingplate and a contact surface of the lower freezing plate; in which thecontact surfaces of the upper and lower freezing plates of the pair offreezing plates are parallel in their freezing position and remainparallel during movement between the loading and the freezing position;in which, in its freezing position, the contact surface of the upperfreezing plate is arranged at an angle which is ≥2° and ≤30° withrespect to the horizontal; wherein movement between the loading andfreezing position of the pair of freezing plates consists of a linear,vertical displacement of the movable freezing plate.
 17. A medicalcontact shock freezer in accordance with claim 16, in which the shockfreezer comprises a first pair of upper and lower freezing plates and asecond pair of upper and lower freezing plates, the first pair beingarranged above the second pair; in which the first pair of upper andlower freezing plates comprises an immobile lower freezing plate and amoveable upper freezing plate; in which the second pair of upper andlower freezing plates comprises an immobile upper freezing plate and amoveable lower freezing plate; and in which, in its freezing position,the contact surface of each of the upper freezing plates is arranged atan angle which is ≥2° and ≤30° with respect to the horizontal.
 18. Amedical contact shock freezer in accordance with claim 17, in which thelower freezing plate of the first pair of freezing plates and the upperfreezing plate of the second pair of freezing plates are provided by asingle, integrated freezing plate.
 19. A medical contact shock freezerin accordance with claim 16, in which in its freezing position, thecontact surface of the upper freezing plate is arranged at an angle ofbetween 3° and 10° to the horizontal.
 20. A medical contact shockfreezer in accordance with claim 16, in which the contact surface of theupper freezing plate and the contact surface of the lower freezing plateare each planar contact surfaces.
 21. A medical contact shock freezer inaccordance with claim 16, in which the pair of freezing plates definesan operating surface which has: a width that is ≥0.4 m and ≤1.6 m; and adepth that is ≥0.5 m and ≤1.1 m.
 22. A medical contact shock freezer inaccordance with claim 16, in which each freezing plate is configured tooperate at a temperature which is ≤−50° C.
 23. A medical contact shockfreezer in accordance with claim 16, in which, in their freezingposition, the contact surface of the upper freezing plate and thecontact surface of the lower freezing plate are each arranged at anangle of about 5° to the horizontal.
 24. A method of shock freezing aplurality of individual bags containing a medical liquid, wherein themethod comprises: arranging the individual bags side by side, adjacentto each other between the upper freezing plate and the lower freezingplate of a contact shock freezer in accordance with claim 1 with theplates arranged in a bag loading position; subsequently closing thefreezing plates to the freezing position by moving the moveable freezingplate to clamp each individual bag in contact with the contact surfaceof the upper freezing plate and the contact surface of the lowerfreezing plate with each individual bag being held in an angled bagconfiguration at an angle which is ≥2° and ≤30° with respect to thehorizontal, and in which closing the freezing plates to the freezingposition by moving the moveable freezing plate to clamp each individualbag in contact with the contact surface of the upper freezing plate andthe contact surface of the lower freezing plate consists of displacingthe moveable freezing plate linearly and vertically; subsequentlyfreezing the medical liquid in each individual bag to a temperature of−20° C. or below through heat exchange between the medical liquid andthe upper and lower freezing plates; subsequently moving the moveablefreezing plate to its loading position and removing the frozen bags fromthe shock freezer.
 25. A method in accordance with claim 24, in whicheach individual bag is held in an angled bag configuration at an angleof between 3° and 10° to the horizontal.
 26. A method in accordance withclaim 25, in which each individual bag is held in its angled bagconfiguration due to angling of the contact surfaces of its upper andlower freezing plates.
 27. A method in accordance with claim 24, inwhich each bag holds a medical liquid selected from blood plasma, abiological preparation and a pharmaceutical preparation.
 28. A method inaccordance with claim 24, in which freezing the medical liquid in eachindividual bag comprises freezing each bag from a temperature of between15° C. and 25° C. to a temperature of −25° C. or below.
 29. A method inaccordance with claim 28, in which the freezing is accomplished in afreezing time of 60 minutes or less.
 30. A method in accordance withclaim 24, in which the individual bags are selected from i) bagscontaining between about 150 ml and 450 ml of blood plasma and ii) bagscontaining between about 750 ml and 950 ml of blood plasma.